Abstract

Introduction: A close link is proposed between smell impairment and Alzheimer's disease (AD) pathogenesis, pointing to the possibility that damaged olfaction may lead to cognitive deterioration. As a step to evaluate this possibility in rodent models, we used behavioral test battery to investigate whether cognitive and anxiety-like behaviors are altered in mice deprived of olfaction.Affective behavior was tested because cognitive deterioration, the canonical symptom of AD, is often accompanied by emotional symptoms called the behavioral and psychological symptoms of dementia (BPSD).Method: For olfactory deprivation, bulbectomy or methimazole-induced epithelial degeneration was used. Then, mice were subjected to behavioral test battery.Results: After olfactory deprivation, anxiety-like behavior emerged, with severer manifestation in bulbectomized than methimazole-treated mice. Avoidance behavior from 2MT, a synthesized derivative of a fox urine component, was suppressed by bulbectomy but exaggerated by methimazole treatment, which suggests that these two procedures differentially impact on olfactory information processing as is implied from the markedly different modes of anatomical damage after these two treatments. Novel object recognition test revealed that cognitive performance was not impaired by either treatment. However, Morris water maze (MWM) test, in which cognition was assessed in a wet, stressful environment, showed that both deprivation procedures worsened cognitive performance. Conclusion:We conclude that the suppressing influence on MWM performance by olfactory deprivation may be related to an elevated vulnerability to stressful environment, drawing the inference that emotional effects of smell impairment might play an important part in the proposed, smell-linked cognitive impairment in AD.